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Early kinetics of innate and adaptive immune responses during Hepatitis B Virus infection
  1. Paola Fisicaro
  1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
    1. Caterina Valdatta
    1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
      1. Carolina Boni
      1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
        1. Marco Massari
        1. Unit of Infectious Diseases, Azienda Ospedaliera S.M.N. di Reggio Emilia, Reggio Emilia, Italy
          1. Cristina Mori
          1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
            1. Alessandro Zerbini
            1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
              1. Alessandra Orlandini
              1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
                1. Luca Sacchelli
                1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
                  1. Gabriele Missale
                  1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
                    1. Carlo Ferrari (cafer{at}tin.it)
                    1. Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

                      Abstract

                      Background and aim: The innate immunity appears to be silent in acutely HBV-infected chimpanzees, as shown by microarray analysis of intrahepatic gene expression. Whether this observation applies also to HBV pathogenesis in man remains undefined. Aim of the study was thus to characterize natural killer (NK) and CD56+ natural T (NT) cell responses early after human HBV infection and their relationship with the induction of adaptive immunity.

                      Methods: Two HBV seronegative blood donors who became HBsAg and HBV-DNA positive but had persistently normal ALT were followed from a very early stage of HBV infection. Phenotype (CD69 and NKG2D) and function (cytotoxicity and IFN-γ production) of NK and NT cells were analyzed. CD4- and CD8-mediated responses were studied in parallel with overlapping peptides covering the overall HBV sequence by ex-vivo ICS for IFN-γ, IL2, IL4 and IL10 and by ex-vivo Elispot for IFN-γ. Healthy subjects, patients with chronic and acute HBV infection were studied for comparison.

                      Results: An early induction of both innate and adaptive responses was observed. NK and NT cells showed a faster kinetics than HBV-specific T cells with an earlier peak of activity, while CD4 and CD8 cell responses mounted with a similar profile, with higher frequencies of IFN-γ producing CD8 cells at the peak of response.

                      Conclusions: The innate immune system is able to sense HBV infection, as shown by the early development of NK and NT cell responses, which likely contribute to contain HBV infection and to allow timely induction of adaptive responses.

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